AIM: No reliable biomarker for renal cell carcinoma (RCC) exists. The purpose of this study was to analyze the value of CpG island hypermethylation of cell-free (cf) circulating serum DNA in patients with RCC as a potential biomarker. PATIENTS AND METHODS: In total 35 patients with RCC and 54 healthy individuals were enrolled in this study. Cell-free DNA (cFDNA) in serum was isolated and digested with methylation-sensitive restriction enzymes (Bsh1236I, HpaII and HinP1I) to quantify the amount of methylated Adenomatosis-poliposis-coli gene (APC), Gluthation-a-transferase-protein 1 gene (GSTP1), ARF tumor suppressor protein gene (p14(ARF)), cyclin-dependent kinase inhibitor 2A (p16), Retinoid-acid-receptor-beta gene (RAR-B), RAS-association domain family-1 gene (RASSF1), Tissue inhibitor of metalloproteinase-gene (TIMP3) and Prostaglandin-endoperoxid synthase 2 (PTGS2) DNA fragments. RESULTS: In 30 of 35 investigated patients with RCC, at least one gene was methylated within the serum cfDNA. The methylation frequency ranged from 14.3% for p14(ARF) to 54.3% for APC. All genes, except p16 and TIMP3, were significantly more frequently methylated in patients with RCC compared to healthy individuals. Receiver operator characteristic analysis showed a high specificity for serum cfDNA methylation [between 85.2% for RAR-B and 100% for p14(ARF)], but the sensitivity was low in single-gene analysis [range-14.3% for p14(ARF) to 54.3% for APC]. The combined analysis of multiple genes increased the diagnostic sensitivity (i.e. APC, PTGS2 and GSTP1, 62.9%) at a high specificity (87%). DNA hypermethylation of APC was correlated with advanced tumor stage. CONCLUSION: The detection of hypermethylated cfDNA in serum may be helpful for the identification of RCC; the combinatorial analysis of multiple genes may increase the diagnostic accuracy.
AIM: No reliable biomarker for renal cell carcinoma (RCC) exists. The purpose of this study was to analyze the value of CpG island hypermethylation of cell-free (cf) circulating serum DNA in patients with RCC as a potential biomarker. PATIENTS AND METHODS: In total 35 patients with RCC and 54 healthy individuals were enrolled in this study. Cell-free DNA (cFDNA) in serum was isolated and digested with methylation-sensitive restriction enzymes (Bsh1236I, HpaII and HinP1I) to quantify the amount of methylated Adenomatosis-poliposis-coli gene (APC), Gluthation-a-transferase-protein 1 gene (GSTP1), ARF tumor suppressor protein gene (p14(ARF)), cyclin-dependent kinase inhibitor 2A (p16), Retinoid-acid-receptor-beta gene (RAR-B), RAS-association domain family-1 gene (RASSF1), Tissue inhibitor of metalloproteinase-gene (TIMP3) and Prostaglandin-endoperoxid synthase 2 (PTGS2) DNA fragments. RESULTS: In 30 of 35 investigated patients with RCC, at least one gene was methylated within the serum cfDNA. The methylation frequency ranged from 14.3% for p14(ARF) to 54.3% for APC. All genes, except p16 and TIMP3, were significantly more frequently methylated in patients with RCC compared to healthy individuals. Receiver operator characteristic analysis showed a high specificity for serum cfDNA methylation [between 85.2% for RAR-B and 100% for p14(ARF)], but the sensitivity was low in single-gene analysis [range-14.3% for p14(ARF) to 54.3% for APC]. The combined analysis of multiple genes increased the diagnostic sensitivity (i.e. APC, PTGS2 and GSTP1, 62.9%) at a high specificity (87%). DNA hypermethylation of APC was correlated with advanced tumor stage. CONCLUSION: The detection of hypermethylated cfDNA in serum may be helpful for the identification of RCC; the combinatorial analysis of multiple genes may increase the diagnostic accuracy.
Authors: Mark W Ball; Michael A Gorin; Gunes Guner; Phillip M Pierorazio; George Netto; Channing J Paller; Hans J Hammers; Luis A Diaz; Mohamad E Allaf Journal: Clin Genitourin Cancer Date: 2016-03-24 Impact factor: 2.872
Authors: Pier Vitale Nuzzo; Jacob E Berchuck; Keegan Korthauer; Sandor Spisak; Amin H Nassar; Sarah Abou Alaiwi; Ankur Chakravarthy; Shu Yi Shen; Ziad Bakouny; Francesco Boccardo; John Steinharter; Gabrielle Bouchard; Catherine R Curran; Wenting Pan; Sylvan C Baca; Ji-Heui Seo; Gwo-Shu Mary Lee; M Dror Michaelson; Steven L Chang; Sushrut S Waikar; Guru Sonpavde; Rafael A Irizarry; Mark Pomerantz; Daniel D De Carvalho; Toni K Choueiri; Matthew L Freedman Journal: Nat Med Date: 2020-06-22 Impact factor: 53.440
Authors: Javier C Angulo; Claudia Manini; Jose I López; Angel Pueyo; Begoña Colás; Santiago Ropero Journal: Cancers (Basel) Date: 2021-04-25 Impact factor: 6.639